In the body, the blood circulates under a certain balance between the coagulation system and the fibrinolytic system.
In the second phase of blood clotting, prothrombin (Factor II), which is one of the blood coagulation factors, is converted into thrombin by the action of thromboplastin (Factor III) in the presence of calcium ions (Ca.sup.2+ ions: Factor IV). In the third phase, fibrinogen (Factor I) is acted upon by the thrombin and changed into strands of fibrin, whereby the blood clotting is completed.
Anticoagulant therapy is given to patients suffering from ischemic heart diseases or patients having a heart valve prosthesis and for the monitoring of the therapy, prothrombin time is measured. The measurement of prothrombin time is carried out by measuring the time required for coagulation by adding thromboplastin, which is an exogenous substance causing blood clotting, to a specimen, whereby the extrinsic coagulation pathway activity can be studied. This method is used for total measurement of extrinsic coagulation factors (Factors I, II, V, VII and X).
Thromboplastin used as a reagent for the above measurement is prepared from an organ-extracted phospholipid so that it differs in the sensitivity according to the products or batches. The measured value therefore does not accurately reflect the amount of coagulation factors in the specimen, which tends to heighten the frequency of hemorrhage caused by excessive administration of an oral anticoagulant and has come to be a serious clinical problem (Poller L. "Progress in standardization in anticoagulant control", Hematol. Rev. 1, 225-241(1987); Latallo Z S, Thomson J M and Poller L, "An evaluation of chromogenic substrates in the control of oral anticoagulant therapy", Br. J. Haematol, 47, 307-318(1981); Poller L. and Taberner D A, "Dosage and control of oral anticoagulants", An international survey, Br. J. Haematol. 51, 479-485(1982)).
An object of the present invention is to overcome the above-described problem by finding a novel prothrombin activator, applying it to the measurement of prothrombin in the blood and thereby providing a reagent for accurate measurement. An another object of the present invention is to apply the reagent to thrombin-related diseases.